Lrp4 in osteoblasts suppresses bone formation and promotes osteoclastogenesis and bone resorption

Proceedings of the National Academy of Sciences of the United States of America

Volumn 112, Issue 11, 2015, Pages 3487-3492

  Xiong, Lei ^a,b   Jung, Ji Ung ^a   Wu, Haitao ^a,c   Xia, Wen Fang ^a   Pan, Jin Xiu ^a   Shen, Chengyong ^a,b   Mei, Lin ^a,b   Xiong, Wen Cheng ^a,b  

^a MEDICAL COLLEGE OF GEORGIA   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

^c INSTITUTE OF BASIC MEDICAL SCIENCES   (China)

Author keywords

LRP4; Osteoblasts; Osteoclasts; Sclerostin; catenin

Indexed keywords

BETA CATENIN; COLONY STIMULATING FACTOR 1; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN 4; MESSENGER RNA; OSTEOCALCIN; OSTEOCLAST DIFFERENTIATION FACTOR; OSTEOPROTEGERIN; SCLEROSTIN; UNCLASSIFIED DRUG; WNT PROTEIN; AMINO ACID; DEOXYPYRIDINOLINE; GLYCOPROTEIN; LOW DENSITY LIPOPROTEIN RECEPTOR; LRP4 PROTEIN, MOUSE; SOST PROTEIN, MOUSE;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BONE MASS; BONE REMODELING; CELL PROLIFERATION; CONTROLLED STUDY; CORTICAL BONE; FEMUR; GENE INACTIVATION; IN VITRO STUDY; LOSS OF FUNCTION MUTATION; MOUSE; NONHUMAN; NULL ALLELE; OSSIFICATION; OSTEOBLAST; OSTEOCLASTOGENESIS; OSTEOLYSIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; TRABECULAR BONE; WNT SIGNALING PATHWAY; YOUNG ADULT; ANIMAL; ANTIBODY SPECIFICITY; BLOOD; BONE DEVELOPMENT; BONE MARROW CELL; CELL DIFFERENTIATION; CELL LINEAGE; DEFICIENCY; KNOCKOUT MOUSE; METABOLISM; MICRO-COMPUTED TOMOGRAPHY; MUSCLE; OSTEOCLAST; PATHOLOGY; RADIOGRAPHY; STROMA CELL;

MUS;

AMINO ACIDS; ANIMALS; BETA CATENIN; BONE MARROW CELLS; BONE RESORPTION; CELL DIFFERENTIATION; CELL LINEAGE; FEMUR; GLYCOPROTEINS; MICE, KNOCKOUT; MUSCLES; ORGAN SPECIFICITY; OSTEOBLASTS; OSTEOCALCIN; OSTEOCLASTS; OSTEOGENESIS; OSTEOPROTEGERIN; RANK LIGAND; RECEPTORS, LDL; STROMAL CELLS; WNT SIGNALING PATHWAY; X-RAY MICROTOMOGRAPHY;

EID: 84925337156     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1419714112     Document Type: Article

References (33)

1. Baron R, Kneissel M (2013) WNT signaling in bone homeostasis and disease: From human mutations to treatments. Nat Med 19(2):179-192.
2. Day TF, Guo X, Garrett-Beal L, Yang Y (2005) Wnt/beta-catenin signaling in mesenchymal progenitors controls osteoblast and chondrocyte differentiation during vertebrate skeletogenesis. Dev Cell 8(5):739-750.
3. Glass DA, 2nd, et al. (2005) Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation. Dev Cell 8(5):751-764.
4. Gong Y, et al. (2001) LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell 107(4):513-523.
5. Little RD, et al. (2002) A mutation in the LDL receptor-related protein 5 gene results in the autosomal dominant high-bone-mass trait. Am J Hum Genet 70(1):11-19.
6. Boyden LM, et al. (2002) High bone density due to a mutation in LDL-receptor-related protein 5. N Engl J Med 346(20):1513-1521.
7. Zhang B, et al. (2008) LRP4 serves as a coreceptor of agrin. Neuron 60(2):285-297.
8. Kim N, et al. (2008) Lrp4 is a receptor for Agrin and forms a complex with MuSK. Cell 135(2):334-342.
9. Weatherbee SD, Anderson KV, Niswander LA (2006) LDL-receptor-related protein 4 is crucial for formation of the neuromuscular junction. Development 133(24):4993-5000.
10. Leupin O, et al. (2011) Bone overgrowth-associated mutations in the LRP4 gene impair sclerostin facilitator function. J Biol Chem 286(22):19489-19500.
11. Choi HY, Dieckmann M, Herz J, Niemeier A (2009) Lrp4, a novel receptor for Dickkopf 1 and sclerostin, is expressed by osteoblasts and regulates bone growth and turnover in vivo. PLoS ONE 4(11):e7930.
12. Semënov M, Tamai K, He X (2005) SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor. J Biol Chem 280(29):26770-26775.
13. Li X, et al. (2005) Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem 280(20):19883-19887.
14. Brunkow ME, et al. (2001) Bone dysplasia sclerosteosis results from loss of the SOST gene product, a novel cystine knot-containing protein. Am J Hum Genet 68(3):577-589.
15. Balemans W, et al. (2002) Identification of a 52 kb deletion downstream of the SOST gene in patients with van Buchem disease. J Med Genet 39(2):91-97.
16. Loots GG, et al. (2005) Genomic deletion of a long-range bone enhancer misregulates sclerostin in van Buchem disease. Genome Res 15(7):928-935.
17. Ahn Y, Sims C, Logue JM, Weatherbee SD, Krumlauf R (2013) Lrp4 and Wise interplay controls the formation and patterning of mammary and other skin appendage placodes by modulating Wnt signaling. Development 140(3):583-593.
18. Wu H, et al. (2012) Distinct roles of muscle and motoneuron LRP4 in neuromuscular junction formation. Neuron 75(1):94-107.
19. Yumoto N, Kim N, Burden SJ (2012) Lrp4 is a retrograde signal for presynaptic differentiation at neuromuscular synapses. Nature 489(7416):438-442.
20. Zhao G, et al. (2000) Targeted overexpression of insulin-like growth factor I to osteoblasts of transgenic mice: Increased trabecular bone volume without increased osteoblast proliferation. Endocrinology 141(7):2674-2682.
21. Cross M, Mangelsdorf I, Wedel A, Renkawitz R (1988) Mouse lysozyme M gene: isolation, characterization, and expression studies. Proc Natl Acad Sci USA 85(17):6232-6236.
22. Kumar J, et al. (2011) LRP4 association to bone properties and fracture and interaction with genes in the Wnt- and BMP signaling pathways. Bone 49(3):343-348.
23. van Bezooijen RL, et al. (2004) Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med 199(6):805-814.
24. Ott SM (2005) Sclerostin and Wnt signaling - the pathway to bone strength. J Clin Endocrinol Metab 90(12):6741-6743.
25. Yasuda H, et al. (1998) Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL. Proc Natl Acad Sci USA 95(7):3597-3602.
26. Teitelbaum SL (2000) Bone resorption by osteoclasts. Science 289(5484):1504-1508.
27. Khan TN, et al. (2013) Cenani-Lenz syndrome restricted to limb and kidney anomalies associated with a novel LRP4 missense mutation. Eur J Med Genet 56(7):371-374.
28. Kariminejad A, et al. (2013) Severe Cenani-Lenz syndrome caused by loss of LRP4 function. Am J Med Genet A 161A(6):1475-1479.
29. Lindy AS, et al. (2014) Truncating mutations in LRP4 lead to a prenatal lethal form of Cenani-Lenz syndrome. Am J Med Genet A 164A(9):2391-2397.
30. Collette NM, et al. (2013) Sost and its paralog Sostdc1 coordinate digit number in a Gli3-dependent manner. Dev Biol 383(1):90-105.
31. Balemans W, et al. (2007) Novel LRP5 missense mutation in a patient with a high bone mass phenotype results in decreased DKK1-mediated inhibition of Wnt signaling. J Bone Miner Res 22(5):708-716.
32. Holdsworth G, et al. (2012) Characterization of the interaction of sclerostin with the low density lipoprotein receptor-related protein (LRP) family of Wnt co-receptors. J Biol Chem 287(32):26464-26477.
33. Chang MK, et al. (2014) Disruption of Lrp4 function by genetic deletion or pharmacological blockade increases bone mass and serum sclerostin levels. Proc Natl Acad Sci USA 111(48):E5187-5195.